a study of the effect of vemurafenib on the pharmacokinetics of acenocoumarol in patients with brafv600 mutation-positive metastatic malignancy

Conditions: Malignant Melanoma, Neoplasms

Summary: this open-label, multicenter, 3-period, fixed-sequence study will evaluate the effect of multiple doses of vemurafenib on the pharmacokinetics of a single dose of acenocoumarol in participants with brafv600 mutation-positive metastatic malignancies. participants will receive a single dose of acenocoumarol 4 mg orally on day 1 and day 23, vemurafenib 960 mg orally twice daily on days 4-26. after completion of pharmacokinetic assessments on day 26, eligible participants will have the option to continue treatment with vemurafenib as part of an extension study (go28399 \[nct01739764\]).


Eligibility criteria:
inclusion criteria: * adult patients, 18-70 years of age * patients with either unresectable stage iiic or iv brafv600 mutation-positive metastatic melanoma or other malignant brafv600 mutation-positive tumor type and who have no acceptable standard treatment options * eastern cooperative oncology group (ecog) performance status 0 to 2 * full recovery from any major surgery or significant traumatic injury at least 14 days prior to the first dose of study treatment * adequate hematologic and end organ function * female patients of childbearing potential and male patients with female partners of childbearing potential must agree to use 2 effective methods of contraception as defined by protocol during the course of the study and for at least 6 months after completion of study treatment exclusion criteria: * prior treatment with vemurafenib or other braf inhibitor within 42 days of day 1 * prior anti-cancer therapy within 28 days (6 weeks for nitrosureas or mitocyn c, or 14 days for hormonal therapy or kinase inhibitors) before the first dose of study treatment day 1 * palliative radiotherapy within 2 weeks prior to first dose of study treatment day 1 * experimental therapy within 4 weeks prior to first dose of study treatment day 1 * history of clinically significant cardiac or pulmonary dysfunction, including current uncontrolled grade \>/=2 hypertension or unstable angina * current grade \>/=2 dyspnea or hypoxia or need for oxygen supplementation * history of myocardial infarction within 6 months prior to first dose of study treatment * active central nervous system lesions (i.e. participants with radiographically unstable, symptomatic lesions) * history of bleeding or coagulation disorders * allergy or hypersensitivity to vemurafenib or acenocoumarol formulations * history of malabsorption or other condition that would interfere with the enteral absorption of study treatment * participants with vkorc1 mutations (1639g\&#8594;a, 1173c\&#8594;t) in either one allele (heterozygous)or two alleles (homozygous) * participants with cyp2c9\*3 mutations in either one allele (heterozygous) or two alleles (homozygous) * history of clinically significant liver disease (including cirrhosis), current alcohol abuse, or active hepatitis b or hepatitis c virus infection * human immunodeficiency virus (hiv) infection requiring antiretroviral treatment, or aids-related illness * pregnant or lactating women